Stratifying patients with gastric cancer according to molecular subtypes could help personalise treatment

medwireNews: Patients with gastric cancer have a different prognosis and response to adjuvant chemotherapy depending on the molecular subtype of the disease, findings indicate.

“This may help clinicians stratify patients according to molecular characteristics and develop tailored treatments for each subtype in future”, the researchers write in Clinical Cancer Research.

They explain that a recent comprehensive analysis by The Cancer Genome Atlas (TCGA) showed that gastric cancer could be classified into four subtypes, namely, Epstein–Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS) and chromosomal instability (CIN), on the basis of genomic and proteomic data.

But as this molecular stratification was based on “highly complicated integrative analysis”, which would be difficult to replicate in the clinic, the study authors used TCGA data to develop a model that could stratify gastric cancer patients in the same way based only on gene expression data.

Applying this model to a cohort of 267 Korean patients who underwent primary gastrectomy between 1999 and 2006, they found that the EBV and GS subtypes were associated with the best and worst prognosis, respectively, in terms of recurrence-free survival (RFS) and overall survival, whereas the prognosis of patients with the MSI or CIN subtype was intermediate.

The results were largely similar in a second cohort of 432 Korean patients diagnosed at the Samsung Medical Center in Seoul, the only exception being that the prognosis of CIN patients was poorer in this cohort than the first cohort, leading the authors to comment that “the CIN subtype might represent a less homogeneous subgroup.”

They also investigated the association between the molecular subtypes and the clinical benefit from adjuvant chemotherapy using data from the 157 patients in the first cohort who had stage II–IV nonmetastatic disease, finding that patients with the CIN subtype appeared to derive the greatest benefit from adjuvant chemotherapy. Specifically, the 3-year RFS rates were 58.7% and 33.5% for those who did versus did not receive chemotherapy, giving a significant hazard ratio for recurrence of 0.39 in favour of chemotherapy.

By contrast, patients with GS tumours derived no benefit from adjuvant chemotherapy, while those with the MSI subtype experienced a moderate benefit, say Ju-Seog Lee, from The University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors. As all EBV patients received adjuvant chemotherapy, there was no comparator group for these patients.

Ju-Seog Lee commented in a press release that “the failure of the GS subtype to respond to chemotherapy was one of the study’s most intriguing findings”, implying that “we need to find novel targets and drugs for this subtype.”

He added that “patients with the GS subtype could now potentially be spared the damaging side effects of chemotherapy that will most likely not work.”